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Biomedical subjects

J Rothwell

Publications and source records attributed to J Rothwell.

50 records · Page 3Linked to original sources

Myoclonus in the rat induced by p,p'-DDT and the role of altered monoamine function.

Administration of p,p'-DDT to rats produced myoclonus, but unlike previous studies in mice, this was not decreased by administration of clonazepam. Precursors of 5-hydroxytryptamine (5-HT) (L-tryptophan and L-5-HTP) reduced the intensity of myoclonus, but the 5-HT agonists, quipazine and Org 6582 did not. Antagonists of 5-HT (methergoline, methysergide and cinanserin) did not potentiate the myoclonus induced by p,p'-DDT. Drugs altering the function of dopamine and noradrenaline (apomorphine, clonidine or phenoxybenzamine) also had no effect on this myoclonus. Administration of monoamine oxidase inhibitors (MAOIs; pargyline, nialamide and tranylcypromine) markedly attenuated the myoclonus, an effect that could not be attributed to an action on any one monoamine system. No observable changes in cerebral biochemical parameters of 5-HT occurred at the onset of myoclonus, although tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) in brain were increased following periods of prolonged myoclonus. Electrophysiological analysis of the myoclonus in the rat induced by p,p'-DDT revealed changes in EEG and EMG activity which suggested an origin for the myoclonus in the brainstem. Although this was similar to electrophysiological findings in some human patients with post-anoxic action myoclonus, the pharmacological studies suggest that the myoclonus induced by p,p'-DDT in the rat is not a suitable model for screening potential drugs to be used in the treatment of this disorder.

Animals↗

Small intestinal permeability in dermatological disease.

Passive small intestinal permeability was investigated in 62 patients with atopic eczema, 29 with psoriasis and 18 with dermatitis herpetiformis, using the cellobiose/mannitol differential sugar absorption test. Urinary recovery of cellobiose and mannitol in patients with both psoriasis and eczema were similar to values in a control population, and were not affected by the extent or activity of skin disease. The cellobiose/mannitol recovery ratio was abnormally high in seven patients with eczema, six of whom underwent jejunal biopsy. Jejunal mucosal morphology was normal in five, and one patient was found to have coeliac disease. Cellobiose/mannitol recovery ratio was also abnormal in seven patients with psoriasis, and in 11 with dermatitis herpetiformis, seven of whom had a normal jejunal biopsy. These findings demonstrate that the passive permeability of the small intestine is normal in the majority of patients with atopic eczema and psoriasis. Increased absorption of macromolecules from the gut lumen cannot be ascribed to defective intestinal integrity, and is unlikely to be relevant to the pathogenesis of eczema. Abnormal intestinal permeability may be a more sensitive manifestation of gluten-sensitive enteropathy than jejunal biopsy in dermatitis herpetiformis.

Adolescent↗

Acute pancreatitis following endoscopic retrograde cholangiopancreatography.

An analysis of endoscopic retrograde cholangiopancreatography (ERCP) examinations suggests that repeated contrast injection into the pancreatic duct during attempts to cannulate the bile duct is of major importance in the aetiology of acute pancreatitis after ERCP, even in the absence of pancreatic acinar opacification. The technique of ERCP can easily be modified to avoid repeated pancreatic duct injection and, by doing so, an increase in the incidence of acute pancreatitis has been reversed.

Acute Disease↗

Metrizamide as contrast medium in endoscopic retrograde cholangio-pancreatography.

Endoscopic retrograde cholangio-pancreatography (ERCP) has been performed in 17 patients using metrizamide (Amipaque) as contrast medium, and in 33 using meglumine diatrizoate (Urografin). The quality of pancreatograms obtained has been compared, using a specially developed scoring system, an any clinical and biochemical evidence of (acute) pancreatitis following ERCP observed. The mean pancreatogram score was slightly higher when Amipaque was used but there was no difference in the frequency or extent of hyperamylasaemia between the two groups. The slight advantage of Amipaque is not sufficient to overcome the disadvantages of its relatively high cost and inconvenience in use.

Cholangiopancreatography, Endoscopic Retrograde↗

Intestinal permeability in coeliac disease: the response to gluten withdrawal and single-dose gluten challenge.

Intestinal permeability has been studied in 21 patients with coeliac disease in relapse and after gluten withdrawal using an oral test of intestinal permeability based on the simultaneous oral administration of two probe molecules. The increased absorption of the larger molecule (cellobiose) and the decreased absorption of the smaller (mannitol) found in untreated coeliac disease both returned to normal within five months of starting treatment, the abnormality in cellobiose absorption correcting more rapidly than that of mannitol. After exposure to a single oral dose of gluten, the intestinal permeability of six patients with treated coeliac disease became transiently abnormal with an increased absorption of cellobiose, returning to normal within one week. The possible structural and functional implications of these findings are discussed. The cellobiose/mannitol ratio appears to be of value in assessing the response to gluten withdrawal in coeliac disease, and also in monitoring patients who are already established on a gluten free diet by detecting dietary lapses and 'non-responding coeliac disease'. It may also offer an alternative to jejunal biopsy in patients subjected to gluten challenge.

Adolescent↗

New disinfecting apparatus for gastrointestinal fibre-endoscopes.

Bacterial contamination of gastrointestinal fibre-endoscopes is a potential source of clinically significant infection. Aqueous 2% alkaline glutaraldehyde adequately disinfects fibre-endoscopes but may cause serious sensitivity reactions among endoscopy staff. A new 'closed-system' disinfecting apparatus is described that disinfects with glutaraldehyde for 30 minutes before an endoscopy session, for two minutes between patient procedures, and for 10 minutes before storage. Bacteriological cultures of the endoscope after disinfection were virtually sterile. Extremely low glutaraldehyde vapour levels were detected by gas chromatography in endoscopy room air during disinfection procedures. This relatively simple apparatus offers rapid, effective, and safe disinfection of fibre-endoscopes.

Disinfection↗

Passive permeability in experimental intestinal damage in rats.

1. Experiments were performed to study the absorption of two simultaneously administered polar probes of different molecular size from closed intestinal loops in rats subjected to various mucosal structural lesions. 2. Absorption of mannitol (molecular radius approximately 0.40 nm) was significantly decreased in rats with villous atrophy and crypt hypoplasia induced by the cytostatic agent methotrexate. The absorption of lactulose (radius approximately 0.54 nm) was also decreased, in contrast to the increased absorption which was found in an earlier study when villous atrophy with crypt hyperplasia was induced by infection by a nematode. The effect of local damage to villous tips, produced by the intraluminal presence of a detergent, was to increase significantly the absorption of lactulose. 3. In conjunction with the findings of earlier studies, these results support the hypothesis that there are at least two routes for the permeation of polar molecules. Small molecules such as mannitol probably pass through numerous cellular pores with a maximum radius lying between 0.40 and 0.54 nm and absorption is closely related to mucosal surface area. Larger molecules such as lactulose are probably restricted to less numerous extracellular pathways and absorption may be related to cell shedding or other areas of mucosal damage.

Animals↗

Small intestinal structure and passive permeability in systemic sclerosis.

Seventeen patients with proven systemic sclerosis had a peroral jejunal biopsy performed. Four biopsies were regarded as showing abnormalities, which were mostly confined to the deeper structures, although in two there was a minimal degree of villous atrophy without epithelial cell changes. Passive intestinal permeability, as assessed by the cellobiose/mannitol test, was normal in all patients. In contrast, seven patients had a low xylose test result, which in five of them could be accounted for by impaired renal function, small intestinal bacterial contamination, or altered gastrointestinal transit. These results indicate that passive intestinal permeability is unaltered in systemic sclerosis, and that malabsorption, when it occurs, is caused by other factors.

Adolescent↗

Intestinal permeability and screening tests for coeliac disease.

In disease states of the small intestine--for example, gluten-sensitive enteropathy--there is an increased permeability to large molecules. This increased permeability extends to polar molecules of intermediate size such as disaccharides, whereas small polar molecules are malabsorbed. A recently-developed oral test, based on the simultaneous administration of two test substances, cellobiose (a disaccharide) and mannitol (a small polar molecule) has been used to investigate permeability in a variety of gastrointestinal diseases, the result of the test being expressed as the ratio (cellobiose/mannitol) of the five hour urinary recoveries of the two probe molecules. Results for patients with pancreatic insufficiency, intestinal bacterial overgrowth, primary hypolactasia, ileocolic or colonic Crohn's disease, and ulcerative colitis were comparable with those in normal controls, whereas in 23 out of 24 untreated coeliacs, and five out of eight patients with Crohn's disease involving the more proximal small bowel, the cellobiose/mannitol ratio was clearly abnormal. A study of its application as a screening procedure for coeliac disease showed that the test was both sensitive and accurate, with fewer false-positive and false-negative results than other recognised screening tests--namely, the xylose test, reticulin antibodies, and blood folate estimations.

Adult↗

Intestinal permeability in rats infected by Nippostrongylus brasiliensis.

Passive intestinal permeability has been investigated in rats infected by the nematode, Nippostrongylus brasiliensis, by the simultaneous administration of two probe molecules. Experiments using a closed intestinal loop show that there is a significantly increased absorption of lactulose and decreased absorption of mannitol in rats at the 10th to 11th day of infection. Experiments using serial oral administration techniques show that these changes start during the second week of the infection with a return towards normal values by the end of the third week. The results are similar to those found in human coeliac disease and add weight to previous studies which have stressed the similarity in the two disease processes.

Animals↗

Abdominal migraine: a cause of abdominal pain in adults?

Eighty-five patients with non-organic abdominal pain, were interviewed with the help of a questionnaire. Those who responded to a high fibre diet were excluded from the study. Twenty-seven patients had multiple pains and 58 described a single pain, which was intermittent in 39. A detailed analysis of the symptoms and family history of the latter group suggested that in 19 patients the symptoms might have been caused by abdominal migraine. Six of these 19 had typical migraine-associated symptoms during the attack, characteristic abdominal pain and a family or personal history of classical migraine. Abdominal migraine should be considered in patients with non-organic abdominal pain where symptoms are not typical of irritable bowel syndrome and when organic disease has been excluded.

Abdominal Pain↗